title: Walking the interactome to identify human miRNA-disease associations through the functional link between miRNA targets and disease genes.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are important post-transcriptional regulators that have been demonstrated to play an important role in human diseases. Elucidating the associations between miRNAs and diseases at the systematic level will deepen our understanding of the molecular mechanisms of diseases. However, miRNA-disease associations identified by previous computational methods are far from completeness and more effort is needed.
  
  
  RESULTS
  We developed a computational framework to identify miRNA-disease associations by performing random walk analysis, and focused on the functional link between miRNA targets and disease genes in protein-protein interaction (PPI) networks. Furthermore, a bipartite miRNA-disease network was constructed, from which several miRNA-disease co-regulated modules were identified by hierarchical clustering analysis. Our approach achieved satisfactory performance in identifying known cancer-related miRNAs for nine human cancers with an area under the ROC curve (AUC) ranging from 71.3% to 91.3%. By systematically analyzing the global properties of the miRNA-disease network, we found that only a small number of miRNAs regulated genes involved in various diseases, genes associated with neurological diseases were preferentially regulated by miRNAs and some immunological diseases were associated with several specific miRNAs. We also observed that most diseases in the same co-regulated module tended to belong to the same disease category, indicating that these diseases might share similar miRNA regulatory mechanisms.
  
  
  CONCLUSIONS
  In this study, we present a computational framework to identify miRNA-disease associations, and further construct a bipartite miRNA-disease network for systematically analyzing the global properties of miRNA regulation of disease genes. Our findings provide a broad perspective on the relationships between miRNAs and diseases and could potentially aid future research efforts concerning miRNA involvement in disease pathogenesis.
authors.affiliation: College of Bioinformatics Science and Technology and State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang 150081, PR China. guoz@ems.hrbmu.edu.cn.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Shi
authors.forename: Juan
authors.initials: J
authors.lastname: Xu
authors.forename: Guangde
authors.initials: G
authors.lastname: Zhang
authors.forename: Liangde
authors.initials: L
authors.lastname: Xu
authors.forename: Chunquan
authors.initials: C
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Guo
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D004194:Disease / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D025941:Protein Interaction Mapping / Q000379:methods*; D013269:Stochastic Processes
chemical_list: D035683:MicroRNAs